Background

We describe two adult brothers with lower limb neuropathy and one with progressive optic neuropathy. One brother was found to have profound biotinidase deficiency by identifying biallelic pathogenic variants of the BTD gene by whole exome sequencing, which was confirmed by markedly decreased serum biotinidase activity.

Case report and methods

The first brother had progressive optic atrophy and vision loss over 10 years and progressive peripheral neuropathy with weakness, pain, and fatigue for 20 years. Profound biotinidase deficiency was also identified in an older brother, who exhibited peripheral neuropathy since four years of age, but had no vision loss.

Results

The first brother's vision loss and neuropathy improved markedly with biotin in six months. However, the neuropathy of the other brother did not improve with 16 months of biotin therapy.

Conclusions

The first brother's neurological issues partially reversed with biotin. However, the longer-term symptoms of the other brother were irreversible. These cases emphasize the importance of considering biotinidase deficiency in the differential diagnosis of adolescents and adults with peripheral neuropathy with or without optic neuropathy/atrophy before symptoms become irreversible. Although WES initially identified the disorder in this family, measuring serum biotinidase activity was a necessary confirmatory step after WES and is less expensive than performing whole exome sequencing.

中文翻译：

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生物素酶缺乏症是成人周围神经病变伴或不伴视神经病变的一种罕见且可能可治疗的原因

背景

我们描述了两名患有下肢神经病变的成年兄弟和一名患有进行性视神经病变的成年兄弟。通过全外显子组测序鉴定BTD基因的双等位基因致病变异，发现一位兄弟患有严重的生物素酶缺乏症，血清生物素酶活性显着降低证实了这一点。

病例报告及方法

第一个兄弟患有进行性视神经萎缩和视力丧失 10 多年，进行性周围神经病变伴虚弱、疼痛和疲劳 20 年。在一个哥哥身上也发现了严重的生物素酶缺乏症，他从四岁起就出现了周围神经病变，但没有视力丧失。

结果

第一个兄弟的视力丧失和神经病变在六个月内使用生物素显着改善。然而，经过 16 个月的生物素治疗，另一个兄弟的神经病变并没有改善。

结论

第一兄弟的神经系统问题被生物素部分逆转。然而，另一个兄弟的长期症状是不可逆转的。这些病例强调了在症状变得不可逆之前，在患有周围神经病变伴或不伴视神经病变/萎缩的青少年和成人的鉴别诊断中考虑生物素酶缺乏的重要性。尽管 WES 最初在该家族中发现了该疾病，但测量血清生物素酶活性是 WES 后必要的确认步骤，并且比进行全外显子组测序更便宜。